Osteomyelitis of the foot is a well-known complication of diabetes mellitus. In this study, the validity of 111In-labeled human nonspecific immunoglobulin G (IgG) scintigraphy was studied in 16 diabetic patients with foot ulcers, gangrene or painful Charcot joints. In all patients, plain radiographs, conventional bone scan images and 111In-IgG images were recorded. The results were verified by histologic examination of surgical specimens in patients who did not respond to antibiotic treatment within 2-3 wk (10 lesions) or long-term clinical follow-up of at least 6-mo (16 lesions). On the bone scans, all seven osteomyelitic foci were detected. However, 19 additional foci not due to osteomyelitis were seen. The absence of true-negative bone scans in this study resulted in a specificity of 0%. On the plain radiographs, four of seven osteomyelitis foci were detected; for 111In-IgG scintigraphy, six of seven (sensitivity 57% and 86%, respectively). Plain radiographs correctly ruled out osteomyelitis in 15 of 19 lesions, 111In-IgG scintigraphy in 16 of 19 (specificity 79% and 84%, respectively). All imaging procedures gave false-positive results in penetrating ulcers over the calcaneus in two patients and in one patient with a Charcot joint, most likely due to recent fractures. A false-negative 111In-IgG study was observed in a patient with severe arterial angiopathy. Accurate estimation of probable osteomyelitis was not possible from the results of soft-tissue cultures, since in only 6 of 12 positive cultures, osteomyelitic foci could be proven. Indium-111-IgG scintigraphy can contribute to adequate evaluation of osteomyelitis in diabetic foot complications because it improves specificity when compared to bone scan and radiographic findings and improves sensitivity in comparison to plain radiographs.